The liver plays an important role in metabolism and detoxification of noxious substances. Harmful stimuli induce inflammation through the release of proinflammatory cytokines such as interleukin-1 beta (IL-1β), tumor necrosis factor–alpha, and interleukin-6. Hepatoprotective agents such as silybin (SB) and the more readily absorbable form, the silybin–phosphatidylcholine complex (SPC), have been used clinically to manage liver disease and oxidative stress. Hepatocytes are the major cellular constituent of the liver but there are also nonparenchymal (NP) cells such as resident monocytes, macrophages, and Kupffer cells. In vivo studies are unable to differentiate whether the hepatic inflammatory response is attributable to all of the cells of the liver or to only parenchymal or NP cells. The present study confirms that some of the antiinflammatory properties seen clinically in both SB and SPC are attributable to liver parenchyma. Hepatocyte cultures were pretreated with SB or SPC and then exposed to IL-1β. The response to IL-1β was compared in the treated versus nontreated cultures. The inflammatory response was measured by production of prostaglandin E2, interleukin-8, and monocyte chemotactic protein–1 and by nuclear factor–kappa B (NF-κB) translocation; IL-1β was found to increase all of these. Pretreatment with SB and SPC significantly inhibited production of the proinflammatory markers and attenuated NF–κB translocation. This study indicates that hepatocytes are a direct target of the pharmacologic action of SB and SPC and confirms that the hepatoprotective effects of these agents may go beyond their action on NP cells of the liver. Study supported by Nutramax Laboratories, Inc
Commentary: SB and the more absorbable SPC have been successfully used clinically to manage liver disease. This study adds to our knowledge about how that happens. Since liver disease is one of the leading causes of nonaccidental death in dogs, it’s good to both have products that are hepatoprotective and understand the ways in which they work.—Patricia Thomblison, DVM, MS
Silybin inhibits interleukin-1β-induced production of pro-inflammatory mediators in canine hepatocyte cultures. Au AY, Hasenwinkel JM, Frondoza CG. J VET PHARMACOL THER 34:120-129, 2011.